POS1263 PRE-EXPOSURE PROPHYLAXIS FOR SARS-CoV-2 INFECTION WITH SUBCUTANEOUS CASIRIVIMAB/IMDEVIMAB IN PATIENTS WITH IMMUNE MEDIATED INFLAMMATORY DISEASES.
Authors: F. Fagni, K. Schmidt, D. Bohr, L. Valor, F. Hartmann, K. Tascilar, K. Manger, B. Manger, A. Kleyer, D. Simon, G. Schett, T. Harrer
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with immune-mediated inflammatory diseases (IMID), particularly if treated with B-cell depleting therapies, show reduced humoral responses to SARS-CoV-2 vaccines and increased risk of severe COVID-19 (1,2). Since pre-exposure prophylaxis (PrEP) with monoclonal antibodies against SARS-CoV-2 proved effective in preventing infection and COVID-19 (3) in the general population, PrEP could be used for passive immunization of vaccine-refractory patients with IMIDs. Objectives To evaluate the persistence of serum and salivary anti-SARS-CoV-2 IgG antibodies in vaccine-refractory patients with IMID after PrEP with casirivimab/imdevimab. Secondary outcomes were safety, SARS-CoV-2 infection, and adverse COVID-19 outcomes. Methods We performed a longitudinal analysis on anti-SARS-CoV-2 IgG titers in IMID patients who received a PrEP with 1200 mg of subcutaneous casirivimab/imdevimab due to high infection risk, as they had not developed an adequate humoral response at least 21 days after three COVID-19 vaccinations (Table 1). Serum and salivary anti-SARS-CoV-2 Spike IgG were quantified by ELISA (EUROIMMUN, Lübeck, Germany) before PrEP and after 1, 14, and 30 days. IgG levels are given as antibody ratios by dividing the optical density of the sample by that of the calibrator. A cutoff of ≥1.1 was considered positive. Safety as well as polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection and adverse COVID-19 outcomes (hospitalization, mechanical ventilation, death) after PrEP were recorded. Table 1. Baseline characteristics. N 26 Age, mean (SD) 54 (14) Sex, n (%) Female 15 (57.7) Male 39 (42.3) Diagnosis, n (%) ANCA-associated vasculitis 10 (38.5) Rheumatoid arthritis 6 (23.1) Immunoglobulin deficiency 4 (15.4) Systemic sclerosis 2 (7.7) Psoriatic arthritis 1 (3.8) Systemic Lupus Erythematosus 1 (3.8) Non-infectious Uveitis 1 (3.8) Multiple sclerosis 1 (3.8) IgG4-related disease 1 (3.8) Autoinflammatory syndrome 1 (3.8) CD20-depletion Rituximab, n (%) 22 (84.6) Other therapies, n (%) Methotrexate 6 (23.1) Immunoglobulins 4 (15.4) Mycophenolate 1 (3.8) Infliximab 1 (3.8) CD19+ lymphocytes/mm 3 , median (IQR) 0 (0-9) Serum total IgG, median (IQR) 894 (745-987) SD, standard deviation; IQR, interquartile range; ANCA, anti-neutrophil cytoplasmic antibodies. Results We obtained 92 serum and 75 saliva samples from 26 participants at four consecutive timepoints (Figure 1). Anti-SARS-CoV-2 IgG titers were observed in serum and saliva samples of all participants from day 1 and throughout 30 days after PrEP independently of diagnosis, therapy, total IgG, and peripheral CD19+ B-cells. Serum IgG increased rapidly at day 1 and plateaued from day 14 to 30 (Figure 1A), reaching similar levels as seen in healthy subjects after full vaccination (1), while saliva IgG increased steadily from administration up to day 14 and plateaued at day 30 (Figure 1B). No side effects were reported. Five patients (19.2%) had a close contact with a SARS-CoV-2-infected person, after which all but one remained asymptomatic and with a negative PCR test. The patient who tested positive developed mild COVID-19 with fever and cough. Figure 1. Temporal pattern and distribution of serum (A) and salivary (B) anti-SARS-CoV-2 IgG levels. Results from individual participants are represented as line (top) and scatter plots (bottom). Horizontal lines represent median values, the dotted horizontal line represents the positivity cutoff of 1.1. ** p =0.0082; *** p &lt;0.001; **** p &lt;0.0001. mAbs: monoclonal antibodies. Conclusion SARS-CoV-2 PrEP induces stable serum and salivary antibody levels in IMID patients who did not respond to COVID-19 vaccination, regardless of pre-existing clinical and serological features. In IMID, PrEP with casirivimab/imdevimab is safe and has the potential to prevent infection and severe COVID-19. References [1]Simon D, et al. Ann rheum dis. 2021;80:1312-1316. [2]Fagni F et al, et al. Lancet Rheumatol. 2021; e724-e736. [3]Flonza I, et al . MedRxiv . 2021. doi: 10.1101/2021.11.10.21265889 Disclosure of Interests None declared